83 - Rho GTP-Binding Proteins

Summary

Remodeling of the endothelial cell (EC) cytoskeleton is central to many functions of the endothelium. The Rho family of small GTP-binding proteins have been identified as key regulators of F-actin cytoskeletal dynamics in a variety of cell types. They integrate signals from soluble mediators interacting with cytokine, growth factor tyrosine kinase, and G-protein–coupled receptors (GPCRs); as well as signals from cell–cell, and cell–matrix protein adhesion molecules. Recently, it has become appreciated that effector molecules downstream of Rho GTP-binding proteins also modulate several other well described cell signaling pathways. We review the role these molecules play in the cell, with a particular focus on the EC.

HISTORY

The Rho family of small GTP-binding proteins, which consists of 22 members, is part of the larger Ras GTP-binding protein superfamily. These approximately 21-kDa proteins cycle between inactive GDP- and active GTP-bound forms to act as a molecular switch in signal transduction pathways. The members of this family are grouped by virtue of a shared structural motif, the Rho insert loop, that is present in the GTPase domain and contributes to the binding specificity for downstream effector molecules (1,2). In addition to this shared structural feature, most Rho family members undergo post-translational modification to link farnesyl or geranylgeranyl groups to the cysteine in a CAAX motif at the C-terminus of the molecule. Subcellular localization of the molecule is directed by the lipid moiety and, in some family members, is also influenced by additional domains in the C-terminus.